There is a clear association between smoking and lung cancer, but it is still not known why some individuals, who are heavily exposed to large concentrations of chemical carcinogens, do not develop tumors, whereas others do. These observations provide circumstantial evidence for the involvement of a genetic factor that predisposes for tumor formation. Recent restriction fragment length polymorphism (RFLP) studies have shown that the loss of normal cellular sequences from chromosome 13 (in the case of retinoblastoma) and chromosome 11 (in the cases of Wilm's tumor and bladder cancer) have been associated with malignancy. It appears that his method might be generally applied to the analysis of inherited susceptibility to cancer and therefore be informative in risk assessment for lung cancer. Tumor and normal tissue form high molecular weight DNA samples have been collected from more than 30 cancer patients for restriction enzyme digestion and Southern analysis. Initial experiments have centered on examination of genes located on the short-arm of chromosome 11; loss of allelic fragments during tumorigenesis have been detected in 15% of samples at the cellular Harvey ras locus and in 13% of samples at the insulin locus. Experiments that examine more than 20 additional genetic loci throughout the human genome for these DNA samples are in parogress.